A structure-toxicity program is proposed which will entail synthesis of informative congeners of perilla ketone and examination of nucleophilic and possible toxicity-related (bio)chemical reactions. This effort will be primarily directed at evaluation of a hypothetical molecular mechanism of toxicity relating the effects of pulmonary-specific furanoid toxins and their possible pyrrolizidine congeners, to the vinyl ether dihydrofuran linkage of the aflatoxins. The isolation and/or synthesis and toxicity evaluation (target tissue, pathology, and LD50 determination) of furanoid natural products is also proposed. Such a concerted program could lead to a greater understanding of the mechanisms of action of these environmental toxins, identify other potential toxicants, and predict dangers associated with yet undiscovered or unsynthesized substances. A limited study of congeners of the highly toxic perilla ketone (PK) indicate that particular structural features make it extremely lung-toxic. Chief among these features appears to be the 3-furyl substitution, reminiscent of the related sweet toxins and the pyrrole metabolites formed from the pyrrolizidine alkaloids. The similarity of structural elements and the possibility of a common mechanism for these substances suggests the importance of understanding more fully their structure-toxicity relationship. Congeners of PK lacking the structural features producing pulmonary effects and many natural, synthetic, and commercial furans retain high toxicity. They are, however, much less potent and lung selective than PK. The fact that both 2- and 3-substituted furans are a ubiquitous, naturally occurring class of potentially toxic and mutagenic heterocycles, suggests they may present a substantial danger to health. In this light, an effort to evaluate other naturally occurring and potentially hazardous furans for toxicity cannot be overemphasized.